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Biomedical subjects

D Clements

Publications and source records attributed to D Clements.

At least 55 records · Page 3Linked to original sources

Squamous carcinoma in the liver.

Squamous carcinoma of the liver has only rarely been reported. We present a case which highlights not only the difficulties in diagnosis but also how it can closely mimic sclerosing cholangitis.

Aged↗

High incidence of poor sulfoxidation in patients with primary biliary cirrhosis.

An impaired sulfoxidation pathway has been implicated in the pathogenesis of chlorpromazine-induced hepatotoxicity. Since some patients with chronic chlorpromazine-induced cholestasis may have features of primary biliary cirrhosis, we studied the ability to sulfoxidate the amino acid analogue S-carboxymethyl-cysteine in 44 patients with primary biliary cirrhosis and in two control groups--one without liver disease and one with a variety of liver diseases other than primary biliary cirrhosis. Poor sulfoxidation was observed in 84 percent of the patients with primary biliary cirrhosis, as compared with 24 percent of patients with other liver diseases and 22 percent of normal controls (P less than 0.0005 for both comparisons). Poor sulfoxidation did not correlate with the degree of hyperbilirubinemia or histologic severity of liver disease in any of the groups studied. There was an inverse correlation with age only in the patients with primary biliary cirrhosis (r = -0.44, P less than 0.001). Liver transplantation was performed in six of the patients and improved sulfoxidation in five; in the four with primary biliary cirrhosis, sulfoxidation improved from poor to good or intermediate. We conclude that poor sulfoxidation is closely associated with primary biliary cirrhosis but not with the other liver diseases we studied.

Adolescent↗

A proposed mechanism for chlorpromazine jaundice--defective hepatic sulphoxidation combined with rapid hydroxylation.

On the basis of previous experimental studies we postulated that individuals who were phenotypically good hydroxylators but poor sulphoxidisers would be susceptible to chlorpromazine jaundice. Sulphoxidation capacity was assessed in 12 subjects with a history of chlorpromazine jaundice, using S-carboxymethyl-L-cysteine as an in vivo probe. Following an oral dose of 750 mg, unchanged compound and sulphoxide metabolites were measured in urine. All 12 subjects (100%) were shown to be poor sulphoxidisers compared to 22% of normal controls (P less than 0.001) and 23.8% of liver disease controls (P less than 0.001). No subjects with a history of chlorpromazine jaundice had an impaired hydroxylation capacity as assessed by recovery of 4-hydroxydebrisoquine in urine following oral debrisoquine. The results support the hypothesis and demonstrate an inherent metabolic basis of susceptibility to chlorpromazine jaundice.

Adult↗

Indocyanine green clearance in acute rejection after liver transplantation.

Previous animals studies have demonstrated a fall in liver blood flow associated with acute rejection after liver transplantation. To study the relationship between rejection and liver blood flow in humans after liver transplantation indocyanine green (ICG) clearance was measured serially in 7 patients with clinical and histological features of acute rejection. There was a consistent pattern of satisfactory initial ICG clearance that fell in association with acute rejection and rose with successful treatment of the episode of rejection. In one patient there was no improvement in ICG clearance after treatment with additional immunosuppression, and she subsequently required retransplantation for chronic rejection. The volume of distribution of ICG was also estimated and fell considerably during the first weeks after transplantation. These results show that rejection is associated with a reduction in ICG clearance that may be due to a fall in liver blood flow, and that graft ischemia and rejection may therefore be interrelated, and important in one another's etiology.

Blood Volume↗

Persistent shigellosis.

Shigella usually causes a self-limited infection which untreated lasts on average seven days (range one to 30 days). We report a patient who had persistent symptoms for 10 months caused by Shigella flexneri which was finally identified on cultures from a rectal swab.

Adult↗

Early onset high grade dysplasia in ulcerative colitis.

We report a patient with ulcerative colitis who underwent colectomy when aged 25 years for multifocal high grade dysplasia which had developed within 2 years of diagnosis, and only 5 1/2 years after his first symptoms. The implications of this case for the management of ulcerative colitis are discussed.

Adult↗

Orthotopic liver transplantation: postoperative complications and their management.

The Birmingham liver transplant programme started in 1982. Forty-six patients have been transplanted with a follow-up of 3 months or longer. Twenty-seven patients are still alive, of whom sixteen have lived for more than one year. The 30 day hospital mortality was 30.4 per cent and the actuarial predicted one year survival 55.5 per cent. Four patients have been regrafted for chronic rejection and graft failure. Thirteen patients have required surgery in the postoperative period for: bleeding (two), removal of abdominal packs (four), biliary leaks and obstruction (five), duodenal perforation (one) and small bowel obstruction (one). Acute rejection was common, occurring in 30 patients and progressing to chronic rejection in 4. Ten patients developed renal failure with an 80 per cent mortality and eleven patients developed grand mal fits. Severe bleeding (greater than 70 units) was associated with previous abdominal surgery and a high mortality (88.9 per cent). Opportunistic fungal infection carried a 100 per cent mortality. Although more than half of all transplanted patients will survive for more than one year, the postoperative period is still one of high morbidity and mortality.

Acute Kidney Injury↗

Comparison of bolus and infusion methods for estimating hepatic blood flow in patients with liver disease using indocyanine green.

A non-invasive method of estimating liver blood flow by a two-compartment pharmacokinetic model of the plasma clearance of indocyanine green has been previously described in normal animals and patients without liver disease. This non-invasive technique has been compared with the conventional method of measuring liver blood flow by hepatic vein catheterisation in 25 patients with liver disease. There was good correlation between the values for indocyanine green clearance, with the infusion method tending to produce slightly higher results. However, there was poor agreement in the measurement of liver blood flow, as the non-invasive technique over-estimated the hepatic extraction ratio and thus underestimated liver blood flow. Therefore, in patients with liver disease the non-invasive method cannot be relied upon or replace hepatic vein catheterisation for the measurement of liver blood flow.

Humans↗

Iodinated cholylglycyltyrosine: a new agent for hepatobiliary imaging.

The characteristics of radiolabelled cholylglycyltyrosine (CGT), a recently synthesised bile acid, were studied. 125I-CGT-Na was found to have a short plasma half-life of 1.6 +/- 0.4 min in rats and 3.1 +/- 0.7 min in dogs. Biliary clearance studies showed the cumulative biliary output of the tracer over 20 min in rats to be 95.7% of the total dose administered, with a mean biliary transit time (50% retention time) of 4.0 +/- 0.1 min, i.e. similar to the biliary kinetics of taurocholate. 131I-CGT-Na proved to be satisfactory for hepatobiliary imaging in rats and dogs at doses of 35 microCi (1.3 MBq) in rats and 90 microCi (3.3 MBq) in dogs. Satisfactory hepatic images were also obtained in rats that had high bilirubin levels produced by obstruction or the recycling of bile. These results show that CGT has better pharmacokinetics than currently used hepatobiliary imaging agents, and that this new compound may be useful in scintigraphy even in the presence of jaundice.

Animals↗